A targetable acid-responsive micellar system for signal activation based high performance surgical resolution of tumors

Tumor-reporting probes are valuable to guide surgical resection of tumor foci elusive to visual inspection. As tumors display distinct arrays of lectins, we herein report the construction and screening of a panel of glycan-displaying smart micelles for tumor illumination in mice. These micelles consist of cores of rhodamine-sultam (RST) responsive to lysosomal acidity and a corona of poly[styrene-alter-(maleic acid)] glycosylated with d-glucosamine, d-mannosamine or d-galactosamine. These nanoscale micelles are nonfluorescent extracellularly and become luminescent within acidic lysosomes, enabling optical tracking of tumor endocytosis of the micelles. In vivo screening revealed high-efficiency uptake and fluorescence activation of galactosylated micelles (RST@P-Gal) by subcutaneous tumor and disseminated liver tumor foci with diameters of 0.1-10 mm, which is significantly below minimal residual cancer (a minimum of 1 cm clearance). This system is readily adapted to illuminate different tumors by expanding the diversity of glycans on the shell. Given the robustness and high performance of this system, lectin-targeted responsive micelles are attractive for diagnosis or surgical ablation of tumors.